Cancers, or malignant tumors, which are characterized by indefinite cell proliferation and cell death, can be classified into three categories: carcinomas, sarcomas, and leukemia. Recent reports reveal that approximately one in eight women contracts breast cancer, and the risk of prostate cancer is about 9.5% among men over 50 years of age (Helzlsouer, K. J. (1994) Curr. Opin. Oncol. 6: 541-548; Harris, J. R. et al. (1992) N. Engl. J. Med. 327: 319-328). Cancer cells are found to exhibit unique gene expression; and dozens of cancer-specific genetic markers, tumor-associated antigens (TAAs), have been identified.
TAAs are surface molecules that are differentially expressed in tumor cells relative to non-tumor tissues. TAAs make tumor cells immunologically distinct from normal cells and provide diagnostic and therapeutic targets for human cancers. Several monoclonal antibodies have been identified which react specifically with cancerous cells such as T-cell acute lymphoblastic leukemia and neuroblastoma (Minegishi, M. et al. (1989) Leukemia Res. 13: 43-51, Takagi, S. et al. (1995) Int. J. Cancer 61: 706-715). In addition, the discovery of high level expression of the HER2 gene in breast tumors has led to the development of therapeutic treatments (Liu, E. et al. (1992) Oncogene 7: 1027-1032; Kern, J. A. (1993) Am. J. Respir. Cell Mol. Biol. 9: 448-454).
TAAs have been characterized either as membrane proteins or altered carbohydrate molecules of glycoproteins and glycolipids, however their functions remain largely unknown. One TAA family, the transmembrane 4 superfamily (TM4SF), usually has four well-conserved membrane-spanning regions, certain cysteine residues and short sequence motifs. There is evidence that TM4SF antigens exist in close association with other important membrane receptors such as CD4 and CD8 of T cells (Imai, T. and Yoshie, O. (1993) J. Immunol. 151: 6470-6481). It is also suggested by the authors that TM4SF antigens may play a role in signal transduction which in turn, affects cell development, activation and motility. Examples of TM4SF antigens include human melanoma-associated antigen ME491, human and mouse leukocyte surface antigen CD37, and human lymphoblastic leukemia-associated TALLA-1 (Hotta, H. et al. (1988) Cancer Res. 48, 2955-2962; Classon, B. J. et al. (1989) J. Exp. Med. 169: 1497-1502; Tomlinson, M. G. et al. (1996) Mol. Immun. 33: 867-872; Takagi, S. et al. (1995) Int. J. Cancer 61: 706-715).
The discovery of proteins related to a human tumor-associated antigen and the polynucleotides which encode them satisfies a need in the art by providing new compositions which are useful in diagnosing, preventing, and treating disorders associated with cell proliferation.